Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors

Oliveira, Suellen D. S.; Oliveira, Nathalia Ferreira de; Meyer‐Fernandes, José Roberto; Savio, Luiz Eduardo Baggio; Ornelas, Flavia G.I.; Ferreira, Zulma S.; Coutinho‐Silva, Robson

doi:10.1016/j.vph.2016.02.005

Cited by 13 publications

(13 citation statements)

References 53 publications

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“…Conversely, P2Y 1 R −/− monocytes showed a robust adhesion to WT endothelial cells after treatment [17]. Moreover, in our model, the knockdown of endothelial P2Y 1 R mimicked the blockage of monocyte adhesion observed with MRS2179 supporting the role of endothelial P2Y 1 R for leukocyte adhesion [24]. Importantly, the treatment of endothelial cells with low concentration (nM) of melatonin prior to stimulation with 2MeSATP prevented P2Y 1 R-mediated leukocyte adhesion to endothelial cells.…”

Section: Discussionsupporting

confidence: 68%

“…Endothelial cells were stimulated with the P2Y 1 R agonist 2MeSATP (60 μM) for 4 h in the presence or absence of the selective P2Y 1 R antagonist MRS 2179 (0.3 μM) or melatonin (30 nM), which were added to samples 30 min before addition of 2MeSATP. Alternatively, cells were incubated with the melatonin MT receptor antagonist luzindole (30 μM) for 30 min, before melatonin and 2MeSATP treatments [24]. To evaluate the importance of intracellular Ca 2+ for leukocyte adhesion, endothelial cells were treated with 3 μM BAPTA-AM (added 30 min before), in the presence or absence of 2MeSATP (60 μM) (37°C, 5% CO 2 ) for 4 h.…”

Section: Adhesion Assaysmentioning

confidence: 99%

“…Endothelial cells (first passage) grown in 6-well plates and treated with melatonin as described above (see Sect. BAdhesion assays^) were washed with PBS and lysed with cold RIPA buffer (1% Nonidet P-40, 0.25% sodium deoxicolate, 150 mM NaCl, 1 mM EDTA, 1 mM PMSF, 1 mM Na 3 VO 4 , 1 mM NaF, 10 μg/mL aprotinin, 10 μg/mL leupeptin and 50 mM Tris-HCl, pH 7.4, 5 min, 4°C) [24]. Cells were scrapped and centrifuged at 8100 g for 20 min at 4°C, and the supernatant was stored in liquid nitrogen until further use.…”

Section: Western Blottingmentioning

confidence: 99%

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The P2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin

Cardoso

Pompeu

2017

Purinergic Signalling

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Extracellular ATP (released by endothelial and immune cells) and its metabolite ADP are important pro-inflammatory mediators via the activation of purinergic P2 receptors (P2Y and P2X), which represent potential new targets for anti-inflammatory therapy. Endothelial P2Y receptor (P2YR) induces endothelial cell activation triggering leukocyte adhesion. A number of data have implicated melatonin as a modulator of immunity, inflammation, and endothelial cell function, but to date no studies have investigated whether melatonin modulates endothelial P2YR signaling. Here, we evaluated the putative effect of melatonin on P2YR-mediated leukocyte adhesion to endothelial cells and TNF-α production, using mesenteric endothelial cells and fresh peripheral blood mononuclear cells isolated from rats. Endothelial cells were treated with the P2YR agonist 2MeSATP, alone or in combination with melatonin, and then exposed to mononuclear cells. 2MeSATP increased leukocyte adhesion to endothelial cells and TNF-α production in vitro, and melatonin inhibited both effects without altering P2YR protein expression. In addition, assays with the Ca chelator BAPTA-AM indicate that the effect of melatonin on 2MeSATP-stimulated leukocyte adhesion depends on intracellular Ca modulation. P2YR is considered a potential target to control chronic inflammation. Therefore, our data unveiled a new endothelial cell modulator of purinergic P2Y receptor signaling.

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Section: Discussionsupporting

confidence: 68%

Section: Adhesion Assaysmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

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The P2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin

Cardoso

Pompeu

2017

Purinergic Signalling

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“…The endothelial expressions of NTPDases 2 and 3 are increased by schistosomal infection along with a higher hydrolysis of ATP, and ADP generation [115] . ADP is the endogenous agonist of P2Y 1 receptor, which is widely expressed through the vascular system [73] , [81] , [111] , [112] .…”

Section: Schistosomiasismentioning

confidence: 98%

“…Endothelial cells from different vascular beds express several subtypes of purinergic P2Y receptors, including P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 and P2Y 11 receptors [73] , [111] , [112] . Moreover, P2X 4 and P2X 7 receptors [73] , [113] , [114] and NTPDases 1, 2 and 3 are also expressed [85] , [115] .…”

Section: Schistosomiasismentioning

confidence: 99%

Purinergic signaling in schistosomal infection

Silva

2016

Biomedical Journal

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Human schistosomiasis is a chronic inflammatory disease caused by blood fluke worms belonging to the genus Schistosoma. Health metrics indicate that the disease is related to an elevated number of years lost-to-disability and years lost-to-life. Schistosomiasis is an intravascular disease that is related to a Th1 and Th2 immune response polarization, and the degree of polarization affects the outcome of the disease. The purinergic system is composed of adenosine and nucleotides acting as key messenger molecules. Moreover, nucleotide-transforming enzymes and cell-surface purinergic receptors are obligatory partners of this purinergic signaling. In mammalian cells, purinergic signaling modulates innate immune responses and inflammation among other functions; conversely purinergic signaling may also be modulated by inflammatory mediators. Moreover, schistosomes also express some enzymes of the purinergic system, and it is possible that worms modulate host purinergic signaling. Current data obtained in murine models of schistosomiasis support the notion that the host purinergic system is altered by the disease. The dysfunction of adenosine receptors, metabotropic P2Y and ionotropic P2X7 receptors, and NTPDases likely contributes to disease morbidity.

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Purinergic receptors and neglected tropical diseases: why ignore purinergic signaling in the search for new molecular targets?

Pacheco

Dantas

Ferreira

et al. 2018

J Bioenerg Biomembr

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Purinergic receptors are widespread in the human organism and are involved in several physiological functions like neurotransmission, nociception, platelet aggregation, etc. In the immune system, they may regulate the expression and release of pro-inflammatory factors as well as the activation and death of several cell types. It is already described the participation of some purinergic receptors in the inflammation and pathological processes, such as a few neglected tropical diseases (NTDs) which affect more than 1 billion people in the world. Although the high social influence those diseases represent endemic countries, most of them do not have an efficient, safe or affordable drug treatment. In that way, this review aims to discuss the current literature involving purinergic receptor and immune response to NTDs pathogens, which may contribute in the search for new therapeutic possibilities.

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Increased expression of NTPDases 2 and 3 in mesenteric endothelial cells during schistosomiasis favors leukocyte adhesion through P2Y1 receptors

Cited by 13 publications

References 53 publications

The P2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin

The P2Y1 receptor-mediated leukocyte adhesion to endothelial cells is inhibited by melatonin

Purinergic signaling in schistosomal infection

Purinergic receptors and neglected tropical diseases: why ignore purinergic signaling in the search for new molecular targets?

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